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Q8NAU1

- FNDC5_HUMAN

UniProt

Q8NAU1 - FNDC5_HUMAN

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Protein

Fibronectin type III domain-containing protein 5

Gene

FNDC5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Irisin: Contrary to mouse, may not be involved in the beneficial effects of muscular exercise, nor in the induction of browning of human white adipose tissue.1 Publication

GO - Biological processi

  1. positive regulation of brown fat cell differentiation Source: UniProtKB
  2. response to muscle activity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Names & Taxonomyi

Protein namesi
Recommended name:
Fibronectin type III domain-containing protein 5
Alternative name(s):
Fibronectin type III repeat-containing protein 2
Cleaved into the following chain:
Gene namesi
Name:FNDC5
Synonyms:FRCP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:20240. FNDC5.

Subcellular locationi

Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Peroxisome membrane By similarity; Single-pass type I membrane protein By similarity
Note: Imported in peroxisomes through the PEX5 receptor pathway.By similarity
Chain Irisin : Secreted
Note: Detected in the blood of individuals subjected to endurance exercise.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini32 – 152121ExtracellularSequence AnalysisAdd
BLAST
Transmembranei153 – 17321HelicalSequence AnalysisAdd
BLAST
Topological domaini174 – 21239CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. extracellular region Source: UniProtKB
  3. integral component of membrane Source: UniProtKB-KW
  4. peroxisome Source: UniProtKB-KW
  5. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Peroxisome, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134924607.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131Sequence AnalysisAdd
BLAST
Chaini32 – 212181Fibronectin type III domain-containing protein 5PRO_0000328971Add
BLAST
Chaini32 – 143112IrisinPRO_0000415857Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi39 – 391N-linked (GlcNAc...)Sequence Analysis
Glycosylationi84 – 841N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

The extracellular domain is cleaved and released from the cell membrane.
N-Glycosylated.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ8NAU1.
PRIDEiQ8NAU1.

PTM databases

PhosphoSiteiQ8NAU1.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in heart. Very low expression, if any, in colon, pancreas and spleen.1 Publication

Inductioni

Has been shown to be up-regulated some twofold by muscular exercise at the mRNA and protein level; this effect has been suggested to be mediated by PPARGC1A (PubMed:22237023). However, up-regulation upon exercise could not be reproduced, at least not at the mRNA level (PubMed:24040023).2 Publications

Gene expression databases

BgeeiQ8NAU1.
CleanExiHS_FNDC5.
GenevestigatoriQ8NAU1.

Organism-specific databases

HPAiHPA051290.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000362570.

Structurei

Secondary structure

1
212
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi38 – 447Combined sources
Beta strandi50 – 556Combined sources
Turni59 – 613Combined sources
Beta strandi62 – 7312Combined sources
Beta strandi77 – 848Combined sources
Beta strandi89 – 924Combined sources
Beta strandi100 – 11112Combined sources
Beta strandi120 – 1234Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4LSDX-ray2.28A/B/C/D/E/F/G/H33-130[»]
ProteinModelPortaliQ8NAU1.
SMRiQ8NAU1. Positions 33-130.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini36 – 12792Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi210 – 2123Microbody targeting signalSequence Analysis

Sequence similaritiesi

Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG87775.
GeneTreeiENSGT00390000004923.
HOGENOMiHOG000082536.
HOVERGENiHBG067308.
InParanoidiQ8NAU1.
OMAiPDENGME.
OrthoDBiEOG7S2206.
TreeFamiTF325415.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR003961. Fibronectin_type3.
IPR013783. Ig-like_fold.
[Graphical view]
PfamiPF00041. fn3. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 1 hit.
PROSITEiPS50853. FN3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8NAU1-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MHPGSPSAWP PRARAALRLW LGCVCFALVQ ADSPSAPVNV TVRHLKANSA
60 70 80 90 100
VVSWDVLEDE VVIGFAISQQ KKDVRMLRFI QEVNTTTRSC ALWDLEEDTE
110 120 130 140 150
YIVHVQAISI QGQSPASEPV LFKTPREAEK MASKNKDEVT MKEMGRNQQL
160 170 180 190 200
RTGEVLIIVV VLFMWAGVIA LFCRQYDIIK DNEPNNNKEK TKSASETSTP
210
EHQGGGLLRS KI
Length:212
Mass (Da):23,659
Last modified:September 5, 2012 - v3
Checksum:iC4A066452A05A134
GO
Isoform 2 (identifier: Q8NAU1-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     180-181: KD → EA
     182-212: Missing.

Note: No experimental confirmation available.

Show »
Length:181
Mass (Da):20,281
Checksum:i36BEE521AFABE5A6
GO
Isoform 3 (identifier: Q8NAU1-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.
     212-212: I → VRARPGPGWATLCLMLW

Note: No experimental confirmation available.

Show »
Length:153
Mass (Da):17,323
Checksum:i4DA2ABEAC5B4D934
GO
Isoform 4 (identifier: Q8NAU1-4) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Note: No experimental confirmation available.

Show »
Length:137
Mass (Da):15,527
Checksum:i1045BF9CE29A41E4
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7575Missing in isoform 3 and isoform 4. 2 PublicationsVSP_032860Add
BLAST
Alternative sequencei180 – 1812KD → EA in isoform 2. 1 PublicationVSP_032861
Alternative sequencei182 – 21231Missing in isoform 2. 1 PublicationVSP_032862Add
BLAST
Alternative sequencei212 – 2121I → VRARPGPGWATLCLMLW in isoform 3. 1 PublicationVSP_032863

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK092102 mRNA. Translation: BAC03806.1.
AC114493 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07499.1.
CH471059 Genomic DNA. Translation: EAX07502.1.
CH471059 Genomic DNA. Translation: EAX07500.1.
BC062297 mRNA. Translation: AAH62297.1.
BX537781 mRNA. Translation: CAD97840.1.
BF221649 mRNA. No translation available.
CCDSiCCDS369.2. [Q8NAU1-1]
CCDS65483.1. [Q8NAU1-3]
RefSeqiNP_001165411.2. NM_001171940.1. [Q8NAU1-2]
NP_001165412.1. NM_001171941.2. [Q8NAU1-3]
NP_715637.2. NM_153756.2. [Q8NAU1-1]
UniGeneiHs.524234.

Genome annotation databases

EnsembliENST00000496770; ENSP00000476320; ENSG00000160097. [Q8NAU1-3]
GeneIDi252995.
KEGGihsa:252995.
UCSCiuc001bwf.2. human. [Q8NAU1-1]
uc001bwg.3. human. [Q8NAU1-3]

Polymorphism databases

DMDMi403314395.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK092102 mRNA. Translation: BAC03806.1 .
AC114493 Genomic DNA. No translation available.
CH471059 Genomic DNA. Translation: EAX07499.1 .
CH471059 Genomic DNA. Translation: EAX07502.1 .
CH471059 Genomic DNA. Translation: EAX07500.1 .
BC062297 mRNA. Translation: AAH62297.1 .
BX537781 mRNA. Translation: CAD97840.1 .
BF221649 mRNA. No translation available.
CCDSi CCDS369.2. [Q8NAU1-1 ]
CCDS65483.1. [Q8NAU1-3 ]
RefSeqi NP_001165411.2. NM_001171940.1. [Q8NAU1-2 ]
NP_001165412.1. NM_001171941.2. [Q8NAU1-3 ]
NP_715637.2. NM_153756.2. [Q8NAU1-1 ]
UniGenei Hs.524234.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
4LSD X-ray 2.28 A/B/C/D/E/F/G/H 33-130 [» ]
ProteinModelPortali Q8NAU1.
SMRi Q8NAU1. Positions 33-130.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000362570.

PTM databases

PhosphoSitei Q8NAU1.

Polymorphism databases

DMDMi 403314395.

Proteomic databases

PaxDbi Q8NAU1.
PRIDEi Q8NAU1.

Protocols and materials databases

DNASUi 252995.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000496770 ; ENSP00000476320 ; ENSG00000160097 . [Q8NAU1-3 ]
GeneIDi 252995.
KEGGi hsa:252995.
UCSCi uc001bwf.2. human. [Q8NAU1-1 ]
uc001bwg.3. human. [Q8NAU1-3 ]

Organism-specific databases

CTDi 252995.
GeneCardsi GC01M033327.
HGNCi HGNC:20240. FNDC5.
HPAi HPA051290.
MIMi 611906. gene.
neXtProti NX_Q8NAU1.
PharmGKBi PA134924607.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG87775.
GeneTreei ENSGT00390000004923.
HOGENOMi HOG000082536.
HOVERGENi HBG067308.
InParanoidi Q8NAU1.
OMAi PDENGME.
OrthoDBi EOG7S2206.
TreeFami TF325415.

Miscellaneous databases

ChiTaRSi FNDC5. human.
GenomeRNAii 252995.
NextBioi 92038.
PROi Q8NAU1.
SOURCEi Search...

Gene expression databases

Bgeei Q8NAU1.
CleanExi HS_FNDC5.
Genevestigatori Q8NAU1.

Family and domain databases

Gene3Di 2.60.40.10. 1 hit.
InterProi IPR003961. Fibronectin_type3.
IPR013783. Ig-like_fold.
[Graphical view ]
Pfami PF00041. fn3. 1 hit.
[Graphical view ]
SMARTi SM00060. FN3. 1 hit.
[Graphical view ]
SUPFAMi SSF49265. SSF49265. 1 hit.
PROSITEi PS50853. FN3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
  2. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Brain.
  5. The Cancer Genome Anatomy Project (CGAP) at the National Cancer Institute
    Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-133 (ISOFORM 1).
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-212 (ISOFORM 2).
    Tissue: Fetal liver.
  7. Cited for: INDUCTION, SUBCELLULAR LOCATION.
  8. Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiFNDC5_HUMAN
AccessioniPrimary (citable) accession number: Q8NAU1
Secondary accession number(s): A6NMC9
, D3DPQ6, Q6P6D9, Q7Z676
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: September 5, 2012
Last modified: November 26, 2014
This is version 107 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3